U.S. patent application number 11/266862 was filed with the patent office on 2007-05-10 for medical devices having particle-containing regions with diamond-like coatings.
Invention is credited to Jan Weber.
Application Number | 20070106363 11/266862 |
Document ID | / |
Family ID | 37948607 |
Filed Date | 2007-05-10 |
United States Patent
Application |
20070106363 |
Kind Code |
A1 |
Weber; Jan |
May 10, 2007 |
Medical devices having particle-containing regions with
diamond-like coatings
Abstract
According to an aspect of the present invention, various medical
devices, including implantable or insertable medical devices, are
provided, which comprise at least one particle-containing region
whose surface is at least partially coated with a diamond-like
coating.
Inventors: |
Weber; Jan; (Maple Grove,
MN) |
Correspondence
Address: |
MAYER & WILLIAMS PC
251 NORTH AVENUE WEST
2ND FLOOR
WESTFIELD
NJ
07090
US
|
Family ID: |
37948607 |
Appl. No.: |
11/266862 |
Filed: |
November 4, 2005 |
Current U.S.
Class: |
623/1.11 |
Current CPC
Class: |
A61L 31/084 20130101;
A61L 27/303 20130101; A61L 29/103 20130101; A61L 2400/12 20130101;
B82Y 30/00 20130101 |
Class at
Publication: |
623/001.11 |
International
Class: |
A61F 2/06 20060101
A61F002/06 |
Claims
1. A medical device comprising: (a) a particle-containing region
that comprises one or more types of particles and (b) a
diamond-like coating on the surface of said particle-containing
region.
2. The medical device of claim 1, wherein the particle-containing
region is a carbon-particle-containing region.
3. The medical device of claim 2, wherein the
carbon-particle-containing region comprises carbon nanotubes.
4. The medical device of claim 2, the carbon-particle-containing
region comprises single wall carbon nanotubes.
5. The medical device of claim 2, wherein said
carbon-particle-containing region is formed on a substrate from a
liquid suspension of carbon-particles.
6. The medical device of claim 5, wherein said substrate is a
medical device or a portion thereof.
7. The medical device of claim 6, wherein said substrate is a
detachable substrate.
8. The medical device of claim 2, wherein said
carbon-particle-containing region is formed from two or more
sheets, each comprising carbon-particles.
9. The medical device of claim 2, wherein the
carbon-particle-containing region ranges from 1 to 100 .mu.m in
thickness.
10. The medical device of claim 2, wherein said device comprises a
plurality of carbon-particle-containing regions.
11. The medical device of claim 1, wherein said diamond-like
coating is a diamond-like carbon coating.
12. The medical device of claim 11, wherein said diamond-like
carbon coating contains an sp.sup.3 to fraction ranging from 60% to
95%.
13. The medical device of claim 11, wherein said diamond-like
carbon coating is formed by a pulsed laser deposition
technique.
14. The medical device of claim 11, wherein said diamond-like
coating ranges from 50 to 100 nm in thickness.
15. The medical device of claim 1, wherein said particle-containing
region comprises a plurality of diamond-like coatings.
16. The medical device of claim 1, wherein said particle-containing
region is disposed over a substrate corresponding to a medical
device or a portion thereof.
17. The medical device of claim 1, wherein said particle-containing
region with diamond-like coating constitutes an entire medical
device.
18. The medical device of claim 1, wherein said device includes a
therapeutic agent disposed beneath or within said
particle-containing region.
19. The medical device of claim 18, wherein said therapeutic agent
selected from anti-thrombotic agents, anti-proliferative agents,
anti-inflammatory agents, anti-migratory agents, agents affecting
extracellular matrix production and organization, antineoplastic
agents, anti-mitotic agents, anesthetic agents, anti-coagulants,
vascular cell growth promoters, vascular cell growth inhibitors,
cholesterol-lowering agents, vasodilating agents, agents that
interfere with endogenous vasoactive mechanisms, and combinations
thereof.
20. The medical device of claim 1, wherein at least a portion of
said medical device is configured for implantation or insertion
into a vertebrate subject.
21. The medical device of claim 1, wherein said medical device is
selected from a guide wire, a balloon, a vena cava filter, a
catheter, a stent, a stent graft, a vascular graft, a cerebral
aneurysm filler coil, a myocardial plug, a heart valve, a vascular
valve, and a tissue engineering scaffold.
22. The medical device of claim 1, wherein the particle-containing
region is a conductive region.
23. The medical device of claim 2, wherein the
carbon-particle-containing region is a conductive region.
24. The medical device of claim 23, wherein the
carbon-particle-containing region that has a conductivity that
ranges from 1.times.10.sup.4 to 1.times.10.sup.6 S/m.
25. The medical device of claim 23, further comprising a power
source, a second conductive region, and a
therapeutic-agent-containing region comprising a charged
therapeutic agent disposed between said second conductive region
and said carbon-particle-containing conductive region, wherein said
device is configured to apply a voltage from said power source
between said second conductive region and said
carbon-particle-containing conductive region.
26. The medical device of claim 25, wherein said second conductive
region is a conductive substrate corresponding to a medical device
or a portion thereof.
27. The medical device of claim 23, further comprising a power
source, a second conductive region, and an electrolyte containing
region comprising an electrolyte disposed between said second
conductive region and said carbon-particle-containing conductive
region, wherein said device is configured to apply a voltage from
said power source between said second conductive region and said
carbon-particle-containing conductive region, said voltage being of
sufficient polarity and magnitude to produce gas bubbles within
said carbon-particle-containing conductive region.
28. The medical device of claim 27, wherein at least a portion of
said medical device is configured for implantation or insertion
into a vertebrate subject.
29. The medical device of claim 28, wherein said medical device is
selected from a catheter, a stent, an aneurysm filler coil, a
guidewire, a septal closure device, an expandable device for
deploying another medical device, and a device for taking biopsy
samples.
Description
FIELD OF THE INVENTION
[0001] This patent application relates to medical devices,
including implantable or insertable medical devices, having
particle-containing regions with diamond-like coatings.
BACKGROUND OF THE INVENTION
[0002] Implantable and insertable medical devices are well known in
the medical community. Many of these devices are configured to
expand upon implantation or insertion into the body. For instance,
angioplasty procedures are well known, in which a catheter is
navigated through a lumen of a vertebrate subject to a site needing
expansion. For example, a distal portion of a catheter containing a
deflated balloon may be directed to an area of an artery that is
substantially blocked, and that may be enlarged upon expansion of
the balloon, typically by a hydraulic or pneumatic mechanism.
[0003] U.S. Patent Appln. Pub. No. 2004/0138733, the entire
disclosure of which is hereby incorporated by reference, describes
medical devices, which include the use of nanopaper for mechanical
actuation. The medical devices may be provided, for example, in the
form of a balloon catheter, in which the nanopaper is mounted about
an electrode and into which an electrically conductive solution is
dispersed. Actuation of the electrode causes generation of bubbles,
which in turn causes the nanopaper, and thus the medical device to
which it is applied, to expand. Whereas inner bubbles are generally
trapped and act to expand the nanopaper, an issue encountered with
devices of this type is that bubbles created at the outer surfaces
may escape into the surrounding media. Without wishing to be bound
by theory, it is believed that, due to the very high surface area
of the carbon nanotubes, bubbles can arise at many locations
throughout the nanopaper. Small bubbles have tremendous inner
pressure. Normally when they contact one another, smaller bubbles
merge to form larger ones as the pressure is decreased inside the
larger bubbles. However in the case of nanopaper, bubbles cannot
merge together due to the network of carbon nanotubes. They can
only merge if they crack open the carbon nantube paper. The bubbles
on the surface of the paper, however, don't have the restriction of
being surrounded by carbon nanotubes and can readily merge together
to become larger. If they get large enough, their upward force (due
to gravity) eventually becomes larger then the adhesion force which
keeps them sticking to the paper surface, and the bubbles depart
from the surface.
[0004] Even if the actuator is sheathed, it is desirable to prevent
bubbles from escaping from the surface as they and expand the
sheath. For example, if the sheath happened to burst, this would
allow the gas between the sheath and the nanopaper to escape into
the body. If this occurs at high pressure, the gas bubbles will
expand due to a drop in pressure and may cause a blockage in the
arteries.
[0005] Other implantable and insertable medical devices are adapted
to achieve enhanced or suppressed interactions with surrounding
cells and tissue. For example, carbon nanotube materials have been
shown to be an ideal matrix for endothelial cell growth. See, e.g.,
"Carbon Nanotube Bucky Paper Scaffold for Retinal Cell
Transplantation," NASA Ames Research Center, including spatial
organization. This is likely due, at least in part, to the
nanostructure and porosity of such materials. For example, it is
known that nanostructured surfaces may directly interact with cell
receptors, thereby controlling the adhesion or non-adhesion of
cells to the surface. It is also noted that carbon nanotube
materials are porous and therefore may allow for the flow of
therapeutic agents, including growth factors and nutrients.
[0006] However, the mechanical robustness of many particle-based
materials, including paper formed from carbon nanotubes, is in need
of enhancement.
SUMMARY OF THE INVENTION
[0007] The invention is directed to medical devices which include a
diamond-like coating over at least a portion of their surfaces.
According to an aspect of the present invention, various medical
devices, including various implantable or insertable medical
devices, are provided, which comprise at least one
particle-containing region whose surface is at least partially
coated with a diamond-like coating. In some embodiments, the
particle-containing region is conductive. In some embodiments, the
particle-containing region contains a therapeutic agent.
[0008] An advantage of this invention is that medical devices
having particle-containing regions may be provided, in which the
robustness of the particle-containing region is improved.
[0009] Another advantage of this invention is that medical devices
having expandable particle-containing regions, for example,
carbon-particle-containing regions, may be provided in which bubble
formation at (and hence bubble loss from) the outer surfaces of the
particle-containing regions is reduced or prevented.
[0010] These and other embodiments and advantages of the present
invention will become readily apparent to those of ordinary skill
in the art upon review of the Detailed Description and Claims to
follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIGS. 1A and 1B are schematic cross-sectional longitudinal
and lateral views, respectively, of a balloon assembly having
actuators on its outer surface, which are depicted in a contracted
or non-actuated state, in accordance with an embodiment of the
present invention. FIGS. 1C and 1D are the views of FIGS. 1A and
1C, respectively, in which the actuators are depicted in an
expanded or actuated state.
[0012] FIGS. 2A and 2B are schematic cross-sectional longitudinal
and lateral views, respectively, of a balloon assembly having
actuators on its outer surface, which are depicted in a contracted
or non-actuated state, in accordance with an embodiment of the
present invention.
[0013] FIGS. 2C and 2D are the views of FIGS. 2A and 2B,
respectively, in which the actuators are depicted in an expanded or
actuated state.
[0014] FIG. 3A is a schematic side view of an actuator, in
accordance with an embodiment of the present invention.
[0015] FIGS. 3B and 3C are schematic side views, illustrating a
process for making the actuator of FIG. 3A.
[0016] FIGS. 3D and 3E are schematic side views, illustrating the
operation of the actuator of FIG. 3A.
[0017] FIGS. 4A and 4B are schematic longitudinal and end views,
respectively, of a stent. FIGS. 4C-4E are cross-sectional views of
a coated wire of the stent of FIGS. 4A and 4B, in accordance with
three different embodiments of the present invention.
[0018] FIG. 5A is a schematic, partial longitudinal view of a stent
wall.
[0019] FIG. 5B is a cross-sectional view of the stent wall
illustrated in FIG. 5A, taken along line I-I, in accordance with an
embodiment of the present invention. FIGS. 5C-5E are
cross-sectional views illustrating a process of making the stent
wall of FIGS. 5A and 5B.
[0020] FIG. 6A is a cross-sectional view of the stent wall
illustrated in FIG. 5A, taken along line I-I, in accordance with
another embodiment of the present invention. FIGS. 6B and 6C are
cross-sectional views illustrating a process of making the stent
wall of FIGS. 5A and 6A.
[0021] FIG. 7 is a schematic view of a process of forming a
carbon-particle-containing region from carbon nanotube sheets.
[0022] FIGS. 8A and 8B are schematic cross-sectional longitudinal
and lateral views, respectively, of a balloon assembly having
actuators on its outer surface, which are depicted in a in an
expanded or actuated state. These drawings are analogous to those
of FIGS. 1C and 1D, except that the assembly is further provided
with an elastic sheath.
DETAILED DESCRIPTION
[0023] A more complete understanding of the present invention is
available by reference to the following detailed description of
various aspects and embodiments of the invention. The detailed
description of the invention which follows is intended to
illustrate but not limit the invention.
[0024] According to an aspect of the present invention, medical
devices, including various implantable or insertable medical
devices, are provided, which comprise at least one
particle-containing region whose surface is at least partially
coated with a diamond-like coating.
[0025] Medical devices which may be provided with such
diamond-coated particle-containing regions include implantable or
insertable medical devices, which can be selected, for example,
from the following: catheters (e.g., renal or vascular catheters
such as balloon catheters), guide wires, balloons, filters (e.g.,
vena cava filters), filter wires, stents (e.g., coronary vascular
stents, peripheral vascular stents, cerebral, urethral, urethral,
biliary, tracheal, gastrointestinal and esophageal stents),
bifurcation stents, stent grafts, stent delivery catheters,
vascular grafts, vascular access ports, embolization devices
including cerebral aneurysm filler coils (including Guglilmi
detachable coils and metal coils), intravascular occlusion devices,
septal defect devices, myocardial plugs, Y-adapters, patches,
pacemakers and pacemaker leads, left ventricular assist hearts and
pumps, total artificial hearts, heart valves, vascular valves,
shunts, drain tubes, urinary sphincters, urinary dilators, penile
prosthesis, distal protection devices, biopsy devices, and any
coated substrate (which may comprise, for example, glass, metal,
polymer, ceramic and combinations thereof) that is implanted or
inserted into the body. Further examples of medical devices include
sutures, suture anchors, anastomosis clips and rings, tissue
staples and ligating clips at surgical sites; cannulae, metal wire
ligatures, orthopedic prosthesis such as bone grafts, bone plates,
joint prostheses, orthopedic fixation devices such as interference
screws in the ankle, knee, and hand areas, tacks for ligament
attachment and meniscal repair, rods and pins for fracture
fixation, screws and plates for craniomaxillofacial repair; dental
devices such as void fillers following tooth extraction and
guided-tissue-regeneration membrane films following periodontal
surgery, tissue bulking devices, and tissue engineering scaffolds
for cartilage, bone, skin and other in vivo tissue
regeneration.
[0026] The diamond-coated particle-containing regions may, for
example, be disposed over all or a portion of a substrate (e.g., a
metallic substrate or a non-metallic substrate, such as a polymeric
or ceramic substrate) that corresponds to a medical device or a
portion of a medical device, or they may constitute the bulk of the
medical device (e.g., in the case of a tissue engineering
scaffold).
[0027] The diamond-coated particle-containing regions may be
provided, for example, within the medical device (e.g., beneath a
hydrogel coating, a balloon, a polymeric sheath, etc.) or at the
medical device surface (e.g., on a balloon surface, a stent
surface, a sheath surface, etc.).
[0028] Particle-containing regions may be employed in medical
devices for a variety of reasons. One specific example of a
particle-containing region is a conductive nanopaper region, which,
as noted above, may be used for mechanical actuation. One specific
example of a medical device that employs such an actuator is shown
in longitudinal and lateral cross-sections, respectively, in FIGS.
1A and 1B. The medical device may comprise an axis 111 and proximal
115 and distal 117 regions. The distal end is the end navigated
through a lumen or other passageway of the body of a human or other
vertebrate subject for the performance of various medical
procedures. Near the distal end 117, a housing 112 (e.g.,
comprising a balloon 120, in the present embodiment) may be
provided, having a proximal end 114 and a distal end 116, which
comprises one or more actuators 130, 150, forming an expandable
assembly 118.
[0029] Although the actuators 130, 150 may appear superfluous in
light of the balloon 120, this is not the case. In particular,
balloon catheters can be described as having a hydraulic actuating
mechanism. Because hydraulic systems are more efficient at larger
dimensions, the present trend to downscale device sizes has created
the need for actuators that efficiently function at very small
diameters. Conductive nanopaper actuators meet this criterion.
[0030] Although FIG. 1B illustrates a first and second actuator
130, 150 diametrically opposed to one another this number and
arrangement is for illustrative purposes only, as particular
embodiments may have any number of actuators in any number of
different arrangements and orientations.
[0031] Embodiments comprising more than one actuator may be
configured so that the individual actuators may be activated
collectively or independently. In some embodiments, multiple groups
of actuators may each be activated collectively, with each group
being capable of being activated independently of the other
groups.
[0032] While an electrically actuated medical device for use in
enlarging lumens is shown (e.g., an angioplasty balloon catheter
system), it is to be understood that electromechanical actuation
may be used in conjunction with essentially any type of medical
device, including those described herein, for which expansion is
useful, such as, for example, expandable stents, aneurysm filler
coils, guidewires, and septal closure devices, expandable devices
for deploying other medical devices, devices for taking biopsy
samples, among many others.
[0033] The particular device illustrated comprises a balloon 120
having an outer perimeter 113. Either pneumatic or hydraulic
balloons may be used, or both. The balloon 120 may comprise an
exterior surface 122 and an interior 124. The device may comprise
an interior tube 126 in the interior 124. The interior tube 126 may
provide one or more apertures 128 that allow inflation media to
enter the balloon 120 from the interior tube 126, i.e., in its role
as an inflation lumen. (Note that, unlike the remainder of the
figure, the interior tube 126 of FIG. 1A is not shown in
cross-section so as to allow the illustration of the apertures 128.
The same applies to FIGS. 1C, 2A, 2C, and 8A below.) The interior
tube 126 may also provide a lumen for a guidewire or other
components including, for example, conductors 142, 144 for
operating the actuators 130, 150. While the balloon 120 is shown
inflated, this is for illustrative purposes only, and in some
embodiments the balloon 120 may be inflated after the actuator 130,
150 is activated or balloon 120 inflation may occur simultaneously
with actuator 130, 150 activation.
[0034] The actuator 130 may comprise a first electrode 132 and a
second electrode 136. Suitable conductive materials for the first
electrode 132 are described below. In some embodiments, the
function of the first electrode 132 may by be performed by a
conductive balloon wall 121. The second electrode 136 may comprise,
for example, a particle-containing conductive region with a
diamond-like coating provided at its outer surface 140, as
described in more detail below. A separator 134, such as one of
those described in more detail below, is provided between the first
132 and second 136 electrodes.
[0035] An electrolyte 138 is provided in the actuator 130 so as to
allow for a completed electrical circuit between the first and
second electrodes 132, 136. The electrolyte 138 may be supported by
a suitable fluid 139 as described below. The electrolyte 138 and
fluid 139 are operatively associated with the separator 134 and
first and second electrodes 132, 136. In the embodiment shown, the
electrolyte 138 provides an ion that allows for formation of a gas
upon activation of the actuator 130, e.g., formation of oxygen,
chlorine, or other gas, causing expansion of the second electrode
136. Being an electrochemical process, gas bubble formation does
not occur at non-conductive surfaces. Consequently, gas bubble
formation is impeded or eliminated at the outer surface, where the
particle-containing conductive region is provided with the
diamond-like coating, which is non-conductive. As noted above,
bubbles created at the outer surfaces are likely to escape into the
surrounding media.
[0036] The first and second electrodes 132, 136 may be operatively
associated with a power source 146 by means of the first and second
electrical conductors 142, 144, respectively. The power source 146
may be immediately adjacent to the actuator 130 or may be present
in a proximal region 115 or distal region 117 of the medical
device. The power source 146 may also be external to the subject
during the medical procedure. The conductors 142, 144 may be formed
of any suitable conductive material, such as those as described
below.
[0037] During operation, the power source 146 may be actuated so as
to apply, via conductors 142 and 144, a voltage that is sufficient
to form bubbles at the second electrode 136, for example, a voltage
on the order of about 1.0 to 1.2 Volts. FIGS. 1A and 1B, are
schematic partial longitudinal and lateral sectional views of the
medical device with the actuators 130, 150 in a non-activated
state. FIGS. 1C and 1D, on the other hand, show the same views with
the actuators 130, 150 in an activated state. As depicted in FIGS.
1C and 1D, activation of the actuator expands the thickness .theta.
of the second electrode 136, which consequently increases the
overall width .phi. of the expandable assembly 118.
[0038] In operation, the medical device of FIGS. 1A-D may be
employed for medical procedures such as, for example, an
angioplasty procedure wherein the assembly 118 is navigated through
a body lumen (not shown) of a vertebrate subject until it is
appropriately positioned, such as within a blocked area of an
artery. Once positioned, the power source 146 directs a voltage
(and passes a current), via conductors 142 and 144, that is
sufficient to form bubbles within the second electrode 136, causing
it to expand. The procedure may also comprise the step of
deactivating the actuators 130, 150 by reversing the voltage
sufficiently such that the electrochemical reactions are reversed
and the bubbles are removed, thereby reversing the expansion of the
actuators 130, 150. On the other hand, actuator may be left in an
activated state indefinitely, although over time the actuator may
return to a deactivated state without reversing potential.
[0039] In some embodiments, the device may be provided with an
elastic sheath 160, as illustrated in FIGS. 8A and 8B. An advantage
of an outer elastic sheath is that it may expand as the second
electrode 136 expands, yet it may also act to recompress the second
electrode 136 to a reduced diameter, which may be approximately its
original diameter before activation. Once back to a reduced
diameter, the assembly 118 may be withdrawn from the lumen, or
reactivated. A sheath is not necessary for reduction of diameter,
but may be used to accelerate collapse.
[0040] In some embodiments, the expansion of the balloon may be
made permanent by means including settable gels and mechanical
mechanisms, such as those described, for example, in U.S. Patent
Appln. Pub. No. 2004/0138733. For example, the balloon may be a
detachable balloon that is used to plug various body lumens, for
example, blood vessels.
[0041] In some embodiments, one or more actuators are disposed not
around an outer perimeter of the balloon 120, but rather within the
interior 124 of the balloon 120, for example, either being disposed
on an inner surface of the balloon wall 121 or disposed around the
interior tube 126 in the interior 124. In either latter case, the
actuator 130 may be deployed when the balloon 120 is in a collapsed
state, in which case the actuator 130 will expand the balloon 120
outward from a fully crimped state to a second partially expanded
state. As its diameter is increased, the balloon 120 enters into a
more efficient operating range, where less pressure is required to
generate the large strains that are afforded by hydraulic/pneumatic
actuation. Hence, in this embodiment, the actuator 130 may improve
the efficiency of the balloon 120. A similar effect may be achieved
where the actuator 130 is provided at an outer surface of the
balloon 120, in which case the actuator 130 may be expanded while
the balloon is in its fully crimped position, then contracted,
followed by expansion of the balloon 120.
[0042] As discussed below, greater dimensional changes may be
achieved in various ways, including using thicker electrodes (i.e.,
thicker particle-containing conductive regions) or by stacking
multiple electrodes (e.g., by using multiple actuators). For
example, FIGS. 2A and 2B are schematic partial longitudinal and
lateral sectional views of a medical device, in a non-activated
state, in which multiple actuators are stacked. FIGS. 2C and 2D, on
the other hand, show the same views with the actuators 130, 150 in
an activated state.
[0043] More specifically, theses drawings show an embodiment
similar to that illustrated in FIGS. 1A-1D, except that the medical
device comprises one or more actuator regions, each containing a
second actuator 150 surrounding a first actuator 130. The first and
second actuators 130, 150 may be separated by a partition 141. The
partition 141 may comprise an insulator or an intervening
separator. An insulator may comprise, for example, a ceramic or a
non-conductive or poorly conductive polymer region (e.g., latex,
rubber, silicon rubber, PEBAX, urethane, PELOTHANE, TECOTHANE,
polyester isobutyl styrene, epoxy, thermoplastic elastomer, etc.).
Examples of separators are described below.
[0044] In the embodiment shown in FIGS. 2A-D, the first and second
actuators 130, 150 have the same orientation (i.e., the first
electrode 132 is beneath the second electrode 136). In other
embodiments, at least one orientation is reversed. Where the
orientation of the inner actuator 130 is reversed, a single first
electrode 132 may be employed between two second electrodes
136.
[0045] In embodiments such as that shown in FIGS. 2A-D, the
actuators 130, 150 may be operatively associated with a power
source so that the actuators may be activated independently or
collectively.
[0046] Any number of actuators may be stacked on one another, with
FIGS. 2A-D depicting two stacked actuators for illustrative
purposes only. Stacked actuator arrangements such as those shown in
respect to the balloon catheter shown may also be employed in other
medical devices for which actuation expansion is desired.
[0047] Actuators in accordance with the present invention,
including those illustrated in FIGS. 1A-1D and 2A-2D, may be formed
using a variety of techniques. As one specific example, a series of
successive deposition steps, including electrochemical deposition,
chemical vapor deposition, and/or physical vapor deposition steps,
may be employed in which first electrode 132, separator 134, second
electrode 136 and diamond-like coating, are deposited over a
permanent or removable underlying substrate.
[0048] As another specific example, the components of the actuator
130, including first electrode 132, separator 134, and second
electrode 136 may be pressed together at elevated temperature
(e.g., between 130.degree. C. and 150.degree. C.) to create a
robust structure. The diamond-like coating may be provided on the
second electrode 136 either before or after pressing. The layers of
the actuator may be hot-pressed together before or after applying
the actuator to a surface 122 of the balloon 120. In some
embodiments, during assembly, polymer components of the actuator
130 (e.g., the separator material) may be compressed near the
melting temperatures of the polymer components to create a more
robust interface.
[0049] Methods for connecting a preformed actuator 130 to the
device (e.g., to balloon 120) include used of adhesives and outer
elastic sheaths. Examples of adhesives include, for example,
cyanoacrylic adhesives, polyurethane adhesives, and UV curable
adhesives, among many others. The actuator may also be sewn to the
balloon 120, attached with clamps, and so forth. The actuator 130
or components thereof may be molded in the shape of a particular
medical device in some embodiments.
[0050] An actuator (with diamond-like coating) for use in the
present invention, as well as in various other applications
requiring an electrochemical actuator, including a method of
forming the same, will now be discussed in conjunction with FIGS.
3A-3D. Turning first to FIG. 3B, a particle-containing conductive
region 336 is provided as shown. If desired a conductor 344 (e.g.,
a metal wire or ribbon) may be embedded within the conductive
region 336. For example, the conductor 344 may be placed between
two or more carbon-nanoparticle-containing sheets (see, e.g., FIG.
7), which are then laminated (e.g., by hot pressing) to form a
carbon-particle-containing conductive region 336, within which
conductor 344 is embedded.
[0051] In a subsequent step, top and bottom surfaces of the
conductive region 336 are provided with a diamond-like coating
336d, for example, using techniques such as those described below.
The resulting structure is illustrated in FIG. 3C. Note that the
diamond-like coating 336d that is applied to the
particle-containing region 336 is typically very thin (i.e.,
thinner than the dimensions of the particles making up the
particle-containing regions). Consequently, the texture and
porosity of the particle-containing region 336 is commonly at least
partially preserved after application of the diamond-like coating
336d. Moreover, techniques for forming diamond-like coatings are
typically line-of-sight, vacuum-based techniques. As a result, the
diamond-like coating 336d generally does not deeply penetrate the
underlying particle-containing region 336.
[0052] Note that the conductive region 336 may be treated to
improve conductivity, for example, using the techniques described
below, either before or after application of the diamond-like
coating 336d.
[0053] The structure of FIG. 3C is then folded and the region
containing the crease is removed (e.g., by cutting the folded
structure at the crease), thereby providing the structure of FIG.
3A. Being porous, this structure may be saturated with an
electrolytic fluid such as those described elsewhere herein.
[0054] At this point, construction of the electrochemical actuator
is essentially complete. Being porous, the upper and lower
conductive regions, 336u and 336l, may function as electrodes
during various electrochemical reactions. Moreover, because they
are provided with non-conductive surface, the porous central and
outer diamond-like coated regions 336dc and 336do will not
participate in these electrochemical reactions. Consequently, gas
bubble formation will not occur and loss of gas at the outer
surfaces may be reduced or eliminated as described above. Also,
because the central diamond-like coated region 336dc (which is
actually two adjacent diamond-like coated regions) is porous and
has a non-conductive surface, it may function as a separator. The
conductors 344 facilitate electrical contact between a source of
electrical potential and the upper and lower conductive regions
336u and 336l, respectively.
[0055] Referring now to FIG. 3D, the actuator 330 of FIG. 3D may be
connected to a source of electrical potential such as a battery
350. Assuming that the battery 350 provides a sufficient voltage,
then gas bubbles will be produced at the electrode 3361 expanding
the actuator 330 as seen in FIG. 3E. If desired the polarity may be
reversed to return the actuator to the non-expanded state like that
of FIG. 3D.
[0056] Particles for use in particle-containing regions in
accordance with the present invention may be comprised of a variety
of materials, including organic and inorganic materials. In certain
embodiments, inorganic materials may be preferred as they are
frequently stable under the conditions associated with the
application of a diamond-like coating. Inorganic materials include
metallic materials (e.g., metals and metal alloys) and non-metallic
materials (e.g., carbon and semiconductors, glasses, ceramics and
various other materials, including a variety of metal- and
non-metal-oxides, various metal- and non-metal-nitrides, carbides,
borides, phosphates, silicates, and sulfides, among others).
[0057] Specific examples of metallic inorganic materials may be
selected, for example, from metals (e.g., biostable metals such as
gold, platinum, palladium, iridium, osmium, rhodium, titanium,
tantalum, tungsten, and ruthenium, and bioresorbable metals such as
magnesium), metal alloys comprising iron and chromium (e.g.,
stainless steels, including platinum-enriched radiopaque stainless
steel), alloys comprising nickel and titanium (e.g., Nitinol),
alloys comprising cobalt and chromium, including alloys that
comprise cobalt, chromium and iron (e.g., elgiloy alloys), alloys
comprising nickel, cobalt and chromium (e.g., MP 35N), and alloys
comprising cobalt, chromium, tungsten and nickel (e.g., L605), and
alloys comprising nickel and chromium (e.g., inconel alloys).
[0058] Specific examples of non-metallic inorganic materials may be
selected, for example, from materials containing one or more of the
following: metal oxides, including aluminum oxides and transition
metal oxides (e.g., oxides of titanium, zirconium, hafnium,
tantalum, molybdenum, tungsten, rhenium, and iridium); silicon;
silicon-based ceramics, such as those containing silicon nitrides,
silicon carbides and silicon oxides (sometimes referred to as glass
ceramics); calcium phosphate ceramics (e.g., hydroxyapatite);
carbon; carbon-based, ceramic-like carbon materials such as carbon
nitrides, and silicate particles including monomeric silicates,
polyhedral oligomeric silsesquioxanes (POSS), and clays. Carbon
particles are particularly beneficial for certain embodiments of
the invention. However, it should be kept in mind that other
particulate materials and regions may be used as well.
[0059] By "carbon particles" is meant particles that contain
carbon, typically containing 50 mol % to 75 mol % to 90 mol % to 95
mol % to 99 mol % or more carbon atoms. Carbon particles for use in
the carbon-particle-containing regions of the present invention may
take on a variety of shapes, including spheres, polyhedral (e.g.,
fullerenes), solid cylinders (e.g., carbon fibers), tubes (e.g.,
carbon nanotubes), plates (e.g., graphite sheets) as well as other
regular and irregular shapes.
[0060] Carbon particles for use in the invention may vary widely in
size. In many embodiments, their smallest dimensions (e.g., the
thickness for plates, the diameter for spheres, regular
polyhedrons, fibers and tubes, etc.) are less than 10 micrometers
(e.g., ranging from 0.5 nm to 1 nm to 10 nm to 100 nm to 1
micrometer to 10 micrometers), whereas additional dimensions (e.g.,
the width for plates, and the length for fibers and tubes) may be
of the same order of magnitude or much larger (e.g., ranging from
0.5 nm to 1 nm to 10 nm to 100 nm to 1 micrometer to 10 micrometers
to 100 micrometers to 1000 micrometers or even more).
[0061] Particularly beneficial carbon particles are those that
comprise molecular carbon that is predominantly in sp.sup.2
hybridized form (i.e., structures in which the carbon atoms are
predominantly connected to three other carbon atoms within a
lattice structure, sometimes referred to as a "grapheme carbon
lattice"). Examples of carbon particles that predominantly comprise
carbon in sp.sup.2 hybridized form include graphite, fullerenes
(also called "buckyballs") and carbon nanotubes. Graphite molecules
contain planar sheets of sp.sup.2 hybridized carbon, whereas
fullerenes and carbon nanotubes contain curved sheets of sp.sup.2
hybridized carbon in the form of hollow polyhedral (e.g., "Bucky
balls") and tubes, respectively. Fullerenes and carbon nanotubes
may be thought of as sheets of graphite that are shaped into
polyhedral and tubes and, in fact, may be made, among other
techniques, by directing a laser at a graphite surface, causing
some of the sheets to be displaced from the graphite, which
subsequently react to form fullerenes and/or nanotubes.
[0062] In certain embodiments of the invention, the
carbon-particle-containing regions contain carbon nanotubes,
typically 50 wt % to 75 wt % to 90 wt % to 95 wt % to 99 wt % or
more carbon nanotubes. Examples of carbon nanotubes include
single-wall carbon nanotubes and multi-wall carbon nanotubes (which
term embraces so-called "few-wall" carbon nanotubes). Specific
examples of nanotubes include single wall carbon nanotubes (SWNTs),
which have inner diameters typically ranging from 0.25 nanometer to
0.5 nanometer to 1 nanometer to 2.5 nanometers to 5 nanometers, and
lengths up to 100 micrometers, for example, lengths ranging from 10
nanometers to 100 nanometers to 1 micron (.mu.m) to 10 microns to
100 microns, and multi-wall carbon nanotubes, which have inner
diameters typically ranging from 2.5 nanometers to 5 nanometers to
10 nanometers, outer diameters of 5 nanometers to 10 nanometers to
25 nanometers to 50 nanometers, and lengths up to 100 micrometers,
for example, lengths ranging from 10 nanometers to 100 nanometers
to 1 micron (.mu.m) to 10 microns to 100 microns.
[0063] SWNTs are particularly preferred for many embodiments of the
present invention, including those where a conductive
particle-containing region is desired. At present, the purest SWNTs
are produced by pulsed laser vaporization of carbon that contains
metal catalysts such as nickel and cobalt. Fullerenes are known to
form when the carbon is vaporized, mixes with an inert gas, and
then slowly condenses. The presence of a metal catalyst, however,
is known to form SWNTs. SWNTs are generally considered to be
individual molecules, yet as noted above, they may grow to be
microns in length. SWNTs may also be produced by other processes
such as arc discharge processes.
[0064] Regardless of the production technique, after formation,
SWNTs are typically purified to remove impurities such as amorphous
carbon and residual metal catalysts, for example, by exposure to
NHO.sub.3 or HNO.sub.3/H.sub.2SO.sub.4, followed by rinsing,
drying, and subsequent oxidation at high temperatures. A specific
technique for providing SWNTs with >99.98 wt % purity (as
measured by ICP analysis) is described in the Oak Ridge National
Laboratory, Laboratory Directed Research and Development Program,
Fy 2003, Annual Report. SWNTs are also commercially available as
aqueous suspensions.
[0065] Regardless of the specific carbon particles selected, the
carbon-particle-containing regions for use in the present invention
will typically comprise 50 wt % to 75 wt % to 90 wt % to 95 wt % to
99 wt % or more carbon particles.
[0066] Carbon-particle-containing regions for use in the present
invention may have various desirable traits, including nonplanar
surface topography, porosity, and conductivity. For example, as
noted above carbon nanotube materials have been shown to be an
ideal matrix for endothelial cell growth, which is likely due, at
least in part, to the nanostructure and porosity of such materials.
Porosity allows for free flow of therapeutic agents, including
growth factors and nutrients, and waste products.
[0067] Where the particle-containing regions are conductive they
may also have the ability to expand substantially under certain
conditions, as discussed further below. Macroscopic electrical
conductivities typically employed for this and other purposes are
generally greater than about 1.times.10.sup.3 Siemens/meter (S/m),
more generally ranging from 1.times.10.sup.4 S/m to
5.times.10.sup.6 S/m. Conductivities may be measured, for example,
using a four probe measurement.
[0068] Particle-containing regions for use in conjunction with the
present invention may be formed using any suitable method for
forming such regions. For example, carbon-particle-containing
regions may be formed by suspending carbon particles (e.g., SWNTs)
in an appropriate fluid (e.g., water, one or more organic solvents
such as toluene or chloroform, or a mixture of water and organic
solvent), which may contain further optional agents as desired such
as surfactants (e.g., Triton X-100, an alkylaryl polyether alcohol
or octyl phenol ethoxylate). SWNT suspensions are commercially
available, for example, from Zyvex, Richardson, Tex., USA and Rice
University, Houston, Tex., USA. The suspension is then brought into
contact with a substrate of choice to form a
carbon-particle-containing region.
[0069] In some embodiments, a particle-containing region is formed
on an underlying substrate, which is (or becomes) part of the
medical device (i.e., a permanent substrate). In other embodiments,
the particle-containing region is formed on a temporary substrate,
from which it is subsequently removed (e.g., by separating the
particle-containing region from the substrate or by sacrificing the
substrate by a process such as dissolution, melting, etc.).
[0070] As a specific example, SWNT suspensions may be sprayed onto
desired substrates (e.g., using single or multi-orifice spray
heads, ink jet, etc.) and the liquid allowed to evaporate (e.g., at
elevated temperatures), thereby forming SWNT layers. The density of
the SWNT layers may be varied, for example, by adjusting the spray
duration, the SWNT concentration, the nozzle pressure, and so
forth, which may cause a variation, for example, in the diameter of
bundles (or so-called "ropes") of SWNTs that are formed.
Alternatively, substrates may be dipped into suspensions of SWNTs
to form SWNT layers. For high density packing of the SWNTs, an
additional step may be taken by compressing the SWNTs.
[0071] As another specific example, carbon particle suspensions
(e.g., SWNT suspensions) may be vacuum-filtered to produce
freestanding carbon-particle-containing sheets, for instance,
so-called "carbon nanotube paper" or "bucky paper," which contains
highly entangled nanotube ropes, as described, for example, in U.S.
Patent Appln. Pub. No. 2004/0138733 and in G. M. Spinks, et al.,
"Pneumatic Actuator Response from Carbon Nanotube Sheets,"
Materials Research Society Symposium Proceedings, Vol. 706, Making
Functional Materials and Nanotubes (Materials Research Society,
Pittsburgh, 2002) pp. Z9.22.1-6, the disclosures of each of which
are hereby incorporated by reference. A typical nanotube paper
produced by such a process is between 15 and 35 microns thick, has
a bulk density of 0.3 to 0.4 grams per cubic centimeter, and has a
four point conductivity on the order of 5,000 S/cm (e.g., 1,000 to
10,000 S/cm). The nanotubes commonly aggregate spontaneously into
bundles or "ropes" of approximately 10 nanometers in diameter and
many microns in length. The nanotube paper may then be peeled from
the filter to produce a freestanding film. Alternatively, a filter
material may be employed that is subsequently sacrificed (e.g., by
dissolution, evaporation, combustion, etc.).
[0072] Other processes for producing carbon nanotube paper are
described, for example, in A. G. Rinzler, J. Liu, et al., "Large
scale purification of single-wall carbon nanotubes: process,
product and characterization," Applied Physics A, A67, 29-37
(1998), K. D. Ausman, et al., "Organic Solvent Dispersions of
Single-Walled Carbon Nanotubes: Towards Solutions of Pristine
Nanotubes," J Physical Chem., 104(38):8911-8915 (2000), and T. V.
Sreekumar, et al., "Single-Wall Carbon Nanotube Films," Chem.
Mater., 15:175-178 (2003), each of which are also expressly
incorporated herein by reference. Commercially available carbon
nanotube layers may also be employed. Once formed or obtained, such
carbon-particle-containing regions may be adhered to a permanent
substrate of choice.
[0073] Alternatively, a permanent substrate (e.g., a medical device
or medical device component, a conductive or non-conductive mesh,
etc.) may be positioned on top of a filter whereby at least part of
the substrate is embedded within the particle-containing region at
the same time as the region is formed. For instance, a tubular
filter may be used in which one initially produces a first
particle-containing layer on the inside of the tubular filter
(e.g., using centrifugal force), after which one positions a
tubular medical device (a stent, for example) within this ensemble,
with close contact being established between the device and the
particle-containing layer. One then repeats the process of making
the particle-containing layer to create a second layer, such that
the device becomes encapsulated between the first and second
layers. In case of a stent having multiple struts or wires, the
struts or wires are surrounded in whole or part by the
particle-containing material. Many stent designs may also be
readily expanded in the tubular filter and thus brought into close
contact with the first layer.
[0074] In certain embodiments of the invention, multiple
particle-containing layers are laminated to form a single
particle-containing region. For example, as schematically
illustrated in FIG. 7, multiple carbon-particle-containing sheets
such as nanotube sheets 736s may be laminated into a single
carbon-particle-containing region 736. Being formed from carbon
nanotubes, the sheets 736s have an intrinsic porosity which is
conveyed to the laminate 736. For example, the sheets 736s may be
stacked and pressed together at elevated temperature to create the
laminate 736. The void space in the laminate 736 may be increased
by providing sheets 736s with a non-planar surface, for example,
with a corrugated or indented surface. Such sheets may be made, for
example, using a filter with corrugations or protrusions or
indentations using the above described techniques, for example.
[0075] Where conductive carbon-particle-containing regions are
employed, various measures may be employed to increase the
conductivity of the same. For example, the
carbon-particle-containing regions may be irradiated with a dose of
radiation (e.g., gamma irradiation) that is sufficient to increase
the conductivity. This may be done either before or after providing
the carbon-particle-containing region with a diamond-like coating
(discussed below in more detail). As another example, the
carbon-particle-containing region may be chemically treated under
conditions sufficient to increase conductivity, likewise either
before or after providing the region with a diamond-like
coating.
[0076] In a specific example, a carbon-nanotube-containing region
is irradiated with approximately 170 kGy of gamma radiation as
described in Skakalova, V., et al. "Gamma-irradiated and
functionalized single wall nanotubes." Diamond Relat. Mater. 13(2):
296-8 (2004). A diamond-like coating is then applied, for example,
as described below. This structure may then be treated with thionyl
chloride, SOCl.sub.2, as described in Urszula Dettlaff-Weglikowska
et al., Abstract HH 13.36 "Enhancement of Conductivity of Bucky
Paper by Chemical Modification" Symposium HH, Functional Carbon
Nanotubes, 2004 MRS Fall Meeting, Boston Mass., USA. As noted
above, diamond-like coatings are typically very thin. Consequently,
the texture and porosity of the underlying
carbon-nanotube-containing region is typically at least partially
preserved, allowing the SOCl.sub.2 to react with the defects on the
carbon nanotubes in the interior of the structure. In addition to
improving conductivity, functionalization with SOCl.sub.2 is also
believed to improve bubble retention within the
carbon-particle-containing region--a desirable trait where the
carbon-particle-containing region is used as an actuator.
[0077] As used herein a "diamond-like coating" is one that, like
diamond, is both hard and non-conductive. As used herein a
"non-conductive" material is one that has a volume resistivity in
excess of 1 ohm-cm. Examples of diamond-like coatings include boron
nitride coatings, boron carbide coatings, and diamond-like carbon
coatings, among others.
[0078] Analogous to carbon, boron nitride forms both hard,
diamond-like sp.sup.3-bonded phases and softer, graphite-like
sp.sup.2-bonded phases. The cubic phase of boron nitride, or cBN,
is reported to be second in hardness only to diamond, with a
Vickers hardness of about 5000 kg mm.sup.-2. Resistivities are on
the order of 10.sup.9 and higher have been reported to for
predominantly cBN films. BN films with a high (>85%) percentage
of the cubic phase may be deposited by a variety of deposition
techniques (e.g., vapor deposition, pulsed laser deposition, etc.),
which may employ energetic particle bombardment. For further
information, see, e.g., P. B. Mirkarimi et al., "Review of advances
in cubic boron nitride film synthesis," Materials Science and
Engineering, R21 (1997) 47-100.
[0079] Boron carbide (B.sub.4C) is the third hardest material after
diamond and cBN, with a highest Vickers hardness (VH) similar to
that of cBN at around 5000 kg mm.sup.-2. Volume resistivity is on
the order of 10.sup.2 Ohm-cm or less. Techniques for forming boron
carbide layers include pulsed laser deposition, chemical vapor
deposition (CVD), magnetron sputtering, and plasma spraying, among
others. For further information, see, e.g., S. Aoqui et al.,
"Preparation of boron carbide thin film by pulsed KrF excimer laser
deposition process," Thin Solid Films 407 (2002) 126-131.
[0080] "Diamond-like carbon coating" is a generic term for a
mixture of sp.sup.2 (as in graphite) and sp.sup.3 (as in diamond)
bonded carbon. It is generally described as hard, amorphous, and
chemically inert. Diamond-like carbon coatings are known to be
biocompatible and they are relatively non-conductive, with
electrical resistivities of 10.sup.9 Ohm-cm and higher being
typical. Typical diamond-like carbon coatings contain 80 mol % to
90 mol % to 95 mol % or more carbon atoms. Consequently, these
coatings may contain other elements, introduced either
unintentionally (e.g., as impurities) or intentionally (e.g., as
dopants).
[0081] Properties of diamond-like carbon coatings generally vary
with the ratio of sp.sup.3 to sp.sup.2 bonding. For example, a
variation in the sp.sup.3 fraction (i.e., the number of sp.sup.3
carbons/(the number of sp carbons+sp.sup.2 carbons)) from 10% to
80% has been reported to correspond to a change in hardness from
about 10 GPa to about 90 GPa. Preferably, the diamond-like carbon
coatings comprise an sp.sup.3 fraction of 50% to 60% to 70% to 80%
or more. In this regard, the term "tetrahedral amorphous carbon"
(ta-C) is sometimes used to refer to diamond-like carbon materials
with a high degree of sp.sup.3 bonding (e.g., greater than or equal
80%, typically 80-90%).
[0082] The diamond-like coating renders the underlying
particle-containing region highly wear resistant. Furthermore,
diamond-like coatings may be quite thin, ranging, for example, from
5 nm up to several micrometers, more typically from 10 nm to 100
nm. Thus, these coatings generally at least partially preserve the
topography of the underlying particle-containing region.
[0083] Diamond-like coatings may be formed using a number of
deposition techniques, including laser plasma deposition (e.g.,
pulsed laser deposition), ion beam deposition, magnetron
sputtering, ion sputtering, plasma activated chemical vapor
deposition, and ion plating. These processes may involve, for
example, deposition from a beam/plume of energized (e.g., 10-500
eV) ions.
[0084] For instance, the deposition of amorphous diamond coatings
on SWNTs is described in A. A. Puretzky et al., "Synthesis and
characterization of single-wall carbon nanotube-amorphous diamond
thin-film composites," Applied Physics Letters, Vol. 81, No. 11, 9
Sep. 2002. Specifically, pulsed laser deposition (PLD) of
tetragonally-coordinated amorphous carbon is performed in vacuum
(.about.10.sup.-5 Torr) using a pyrolytic graphite target
irradiated at 193-nm with an ArF-excimer laser (energy density
F.about.1.8 J/cm.sup.2), which generates a plume that contains
carbon ions having kinetic energies up to 100 eV.
[0085] Diamond-like coatings have also been applied to polymers. In
this regard, Mark S. Hammond and A. Wesley Moorehead of SI Diamond
Technology, Inc. have reported the use of a diamond like carbon
coating material, Amorphic Diamond.TM., which comprises nodules of
carbon that have the molecular/crystalline structure of diamond,
with sizes of 100 to 200 nm, densely and uniformly packed in a net
of amorphous carbon polytypes. This material is reported to be able
to withstand flexure and shock without cracking, and it can be
applied to plastic, polymer, metal, and ceramic substrates.
[0086] One could introduce a polymer inside of a carbon paper
structure after a diamond like coating has been applied, for
example, by dip coating or spraying a dissolved polymer,
polymerizing a monomer in a plasma process, by applying a thin
polymer film onto the carbon paper structure and melting the
polymer into the top layer of the paper.
[0087] The unique properties of carbon-particle-containing regions
with diamond-like coatings (also referred to herein as a
"diamond-coated carbon-particle-containing regions"), including
their flexibility, wear resistance, surface texture and porosity,
as well as their conductivity characteristics, render them useful
for a broad range of medical device applications.
[0088] Specific embodiments of medical devices in accordance with
the present invention will now be described in conjunction with
FIGS. 4A and 4B, which are schematic, longitudinal and end views,
respectively, of a stent 400, which is made up of a plurality of
helically woven coated wires 415. Although a woven stent is
illustrated, the invention is applicable to other stent designs,
including laser cut stent designs, among others.
[0089] In one embodiment, illustrated in FIG. 4C, a cross-sectional
view of the coated wires 415 reveals a metallic (e.g., stainless
steel, nitinol, etc.) or non-metallic (e.g., polymer, ceramic,
etc.) wire core 410, covered with a particle-containing layer 436
having a diamond-like coating 436d. The wire core 410 acts as a
permanent substrate for the diamond-coated particle-containing
layer 436,436d. Techniques for providing the diamond-coated layer
436,436d are described above and include spraying with or dipping
in a carbon particle suspension to form the
carbon-particle-containing layer 436, followed by deposition of the
diamond-like coating 436d, among other techniques. The
particle-containing layer 436, the diamond-like coating 436d, or
both, may be provided over the wire core 410 before the stent 400
is formed (e.g., by weaving/braiding the wires), or they may both
be formed after the stent 400 is formed.
[0090] Although the substrate in this particular embodiment is a
stent wire core 410, clearly the diamond-coated layer 436,436d may
be applied to practically any suitable medical device substrate,
including substrates corresponding to all or a portion of the
various medical devices described above.
[0091] As indicated above, diamond-coated particle-containing
regions are desirable for a wide range of medical devices because,
among other things, they may be biocompatible, wear resistant,
flexible, porous, and have a surface topography that may influence
cell growth.
[0092] Where porous, the diamond-coated particle-containing regions
are capable of acting as reservoirs or metering membranes for
therapeutic agents. For example, the therapeutic agent may be
provided beneath the diamond-coated particle-containing regions,
within the non-diamond-coated portions of the particle-containing
regions, and/or within the diamond-coated portions of the
particle-containing regions.
[0093] Numerous therapeutic agents which may be disposed beneath or
within the diamond-coated particle-containing layers of present
invention are described in paragraphs [0040] to [0046] of commonly
assigned U.S. Patent Application Pub. No. 2003/0236514, the entire
disclosure of which is hereby incorporated by reference. A few
specific examples of therapeutic agents for use in conjunction with
medical devices in accordance with the present invention, including
drug eluting catheters and stents, include paclitaxel, sirolimus,
everolimus, tacrolimus, Epo D, dexamethasone, estradiol,
halofuginone, cilostazole, geldanamycin, ABT-578 (Abbott
Laboratories), trapidil, liprostin, Actinomcin D, Resten-NG, Ap-17,
abciximab, clopidogrel, Ridogrel, beta-blockers, bARKct inhibitors,
phospholamban inhibitors, and Serca 2 gene/protein among
others.
[0094] Hence, one or more therapeutic agents may be provided within
(or beneath) the diamond-coated particle-containing layers of the
present invention, including within the diamond-coated
particle-containing layer 436, 436d of FIG. 4C.
[0095] The embodiment illustrated in cross-section in FIG. 4D is
similar to that of FIG. 4C described above, except that a
therapeutic-agent-containing region 412 is supplied between the
wire core 410 and the particle-containing region 436. The
therapeutic agent may be present in substantially pure form or may
be present within a carrier material, for example, a polymer or
polymer blend. Suitable polymers and polymer blends may be
selected, for example, from those listed in paragraph [0054] of
U.S. Patent Application Pub. No. 2003/0236514. This document also
describes various ways of providing therapeutic-agent-containing
regions over a substrate, including thermoplastic and solvent-based
processing techniques. Once a core 410 with
therapeutic-agent-containing region 412 is provided, then a
particle-containing layer 436 and a diamond-like coating 436d may
be created over the therapeutic-agent-containing region 412, for
example, using techniques such as those described above.
[0096] In certain embodiments, the following materials may be
utilized for the device illustrated in FIG. 4D: an electrically
conductive wire core 410, such as metal or metal-alloy wire, a
therapeutic-agent-containing region 412 that (i) contains
containing a mobile, charged therapeutic agent (e.g., either a
therapeutic agent that is inherently charged, or one that is
modified to comprise a charged group) and (ii) is sufficiently
non-conductive to prevent an electrical short from occurring
between the conductive wire core 410 and a conductive
particle-containing layer 436 at voltages effective to promote
migration of the charged therapeutic agent. In these embodiments,
the wire core 410 and the conductive particle-containing layer 436
are connected to a source of electrical potential, which creates an
electric field across the therapeutic-agent-containing region 412.
Consequently, the charged therapeutic agent is driven either toward
the wire core 410 or toward the conductive particle-containing
layer 436, depending on the bias that is applied. In this way,
therapeutic agent delivery may be assisted, hindered, or hindered
and then assisted, as desired. The power source may supply a
constant voltage, a pulsed voltage or both. Where a pulsed voltage
of sufficient magnitude is applied, electroporation of surrounding
cells/tissue may be achieved. Although this above embodiment
concerns a stent formed from conductive wires, the same effect may
be achieved with essentially any medical device, so long as the
therapeutic-agent-containing region is provided between a
conductive member and a conductive particle-containing region.
[0097] In accordance with other embodiments, the core 410
illustrated in FIG. 4C may be made out of a sacrificial material.
This structure may then be provided with a particle-containing
layer 436 and a diamond-like coating 436d, after which the core 410
may be dissolved and then replaced by a therapeutic-agent
containing region 412 (see, e.g., FIG. 4E). This may be especially
useful where a therapeutic agent is employed that can not survive
the diamond-like coating process conditions.
[0098] In still other embodiments of the invention, diamond-coated
particle-containing regions in accordance with the invention are
used to encapsulate pockets of therapeutic agents within one or
more apertures (e.g., mechanically or laser cut apertures), which
apertures may extend partially or completely through a medical
device surface.
[0099] For example, FIG. 5A is a schematic, partial longitudinal
view of a stent wall 500, which is covered with at least one
diamond-coated particle-containing region. The diamond-like coating
536d is illustrated in FIG. 5A, along with the underlying stent
structure 510 (depicted by dashed/hidden lines).
[0100] FIG. 5B is a cross-sectional view of the stent wall 500
illustrated in FIG. 5A, taken along line I-I, in accordance with
one embodiment of the invention. FIG. 5B shows stent struts 510,
which may be formed, for example, from any suitable metallic or
non-metallic material. Between the stent struts 510 are provided
various therapeutic-agent-containing regions 512. The therapeutic
agent may be present in the regions 512 in substantially pure form
or within a carrier material. Examples of suitable therapeutic
agents and carrier materials are set forth above. The struts 501
and therapeutic-agent-containing regions 512 are sandwiched between
two particle-containing layers 536, each having a diamond-like
coating 536d, which correspond to the inner and outer surfaces of
the stent wall 500.
[0101] Numerous techniques are available for forming the structure
of FIGS. 5A and 5B. One such method is described in conjunction
with FIGS. 5C-5E. For example, in a first step, a removable
material 514 is first provided between the struts 510, as
illustrated in FIG. 5C. Examples of such removable materials
include materials that may be removed by any suitable process such
as melting, sublimation, combustion, dissolution or other process
which selectively removes the material without destroying other
portions of the structure. For instance, in some embodiments, the
removable material 514 is made from a material that melts at
moderately elevated temperatures (e.g., 60.degree. C.), for
instance, dental waxes such as those available from MDL Dental
Products, Inc., Seattle, Wash., USA. Other examples of removable
material 514 are materials that are essentially insoluble in cold
water, but are soluble in hot water. Polyvinyl alcohol (PVOH) is
one example of such a material.
[0102] Once the removable material 514 is in place, a
particle-containing layer 536 is applied over the structure of FIG.
5C, to produce the structure illustrated in FIG. 5D. Such a layer
536 may be applied as described above, for example, by spraying a
carbon nanotube suspension over the structure of FIG. 5C.
[0103] The removable material 514 is then removed from the
structure of FIG. 5D and replaced with therapeutic-agent-containing
regions 512, which may be, for example, made entirely of
therapeutic agent or may comprise a therapeutic agent dispersed
within another medium. For example a fluid containing one or more
dissolved and/or dispersed therapeutic agents and an optional
carrier, such as a therapeutic-agent-containing polymer melt, may
be applied to fill the recesses created by the removal of removable
material 514, followed by solidification of the fluid, and removal
of solidified material (if any) from the upper surfaces of the
strut 510, resulting in the structure of FIG. 5E. As another
example, the voids created by removal of removable material 514 may
be filled with a particulate material that consists of or contains
the therapeutic agent.
[0104] Regardless of how the voids are filled, an additional
particle-containing layer 536 is then applied opposite the
previously established layer 536, for example, using techniques
such as those described above. Finally, the top and bottom
particle-containing layers 536 are provided with a diamond-like
coating 536d, again using techniques such as those described above,
thereby producing a structure in accordance with FIG. 5B.
[0105] In other embodiments, for example, where a therapeutic agent
is employed that cannot survive the diamond-like coating process
conditions, the removable material may be removed and replaced with
the therapeutic agent after the formation of the top and bottom
particle-containing layers and diamond-like coating.
[0106] In other embodiments, a medical device is provided which has
apertures that do not extend completely through the same. For
example, FIG. 6A illustrates an embodiment of the invention
analogous to that of FIG. 5B, except that the apertures 610a within
the medical device struts 610 do not extend completely through the
struts 610. Hence, only a single particle-containing layer 636 with
diamond-like coating 636d is required to encapsulate the
therapeutic-agent-containing regions 612.
[0107] Such a device may be made in a fashion similar to that
described in FIGS. 5A-5E. For example, struts 610 having apertures
610a may be provided as illustrated in FIG. 6B. As shown in FIG.
6C, these apertures are then filled with
therapeutic-agent-containing regions 612, for example, as described
above. Then, a particle-containing layer 636 is applied over the
structure of FIG. 6C, followed by deposition of a diamond-like
coating 536d, for example, using techniques such as those described
above, thereby producing a structure in accordance with FIG. 6A.
Also as above, where a therapeutic agent is employed that cannot
survive the diamond-like coating process conditions, the removable
material may be removed and replaced with the therapeutic agent
after the formation of the particle-containing layer and
diamond-like coating. As elsewhere herein, despite the fact that
the above embodiments concern stent struts having multiple partial
or complete apertures, this is for illustrative purposes only and
the same result may be achieved with essentially any medical device
having a substrate with one or more complete or partial
apertures.
[0108] In other embodiments, diamond-coated particle-containing
regions are used as outer coatings for bioerodible stents made, for
example, from a bioerodible polymer or a bioerodible metal, such as
magnesium, iron, or their alloys. In this way, a coating is
provided which surrounds the bioerodible material while at the same
time allowing erosion to proceed. Any particles escaping from the
main stent structure during degradation are captured within the
coating. As indicated elsewhere herein, therapeutic agents may be
provided within the coating, where desired. Where the coating is
diamond-coated, carbon-nanotube-containing region, after the stent
has completely degraded, one is left with a structure consisting of
the carbon nanotubes, some of which are diamond-coated.
[0109] As indicated above, certain embodiments of the invention
make use of the fact that particle-containing conductive regions
like those described herein are known to be useful for purposes of
electromechanical actuation, for example, where
carbon-particle-containing conductive regions are employed. See,
e.g., Spinks et al. above and U.S. Patent Appln. Pub. No.
2004/0138733.
[0110] In these embodiments, a power source is used to provide a
voltage across at least first and second electrodes, which are in
electrically bridged to one another by an electrolyte and
supporting medium. In order to prevent shorting, a separator may be
provided between the electrodes. For example, with reference to
FIGS. 1A-1D, actuator 130 of this device comprises a first
electrode 132, a separator 134, and a second electrode 136.
[0111] More particularly, the first electrode may comprise any
conductive material suitable for functioning as an anode and/or
cathode in the electrochemical reactions that take place during the
course of activation or de-activation. Examples of conductive
materials include suitable members of the following: metals and
metal alloys (e.g., gold or platinum, due to their high
conductivity, oxidation resistance, and radiopacity, which
facilitates visibility of the device during fluoroscopy or the
like), carbon-particle-containing conductive materials and
conductive polymers, and among many other materials.
[0112] The second electrode may comprise a particle-containing
conductive region with a diamond-like coating as described herein.
For actuators, the thickness of the particle-containing conductive
region may vary widely, for example, ranging from 1 to 100 .mu.m.
Single or multiple particle-containing conductive regions may be
employed in a given electrode, for example, arranged laterally or
stacked in order to achieve greater dimensional changes. Greater
dimensional changes may also be achieved by stacking multiple
actuators.
[0113] The separator, where employed, may be selected from various
separators known in the electrochemical arts, and is typically
formed from a material that serves to prevent the first and second
electrodes from shorting, while at the same time allowing transport
of charged species between the same, thereby closing the electrical
circuit between the electrodes. Examples of separator materials
include proton exchange membranes (PEMs). PEMs that may be utilized
include, for example, Nafion (which, for example, may comprise a
perfluorinated ion-exchange solution), and ionomers such as
sulfonated poly(styrene-isobutylene-styrene) (S-SIBS). Nafion
products, including membranes and ion-exchange solutions are
available from ElectroChem, Inc., Woburn, Mass., USA. Details and
use of S-SIBS is provided in "Transport Properties of Triblock
Copolymer Ionomer Membranes For Fuels Cells," Y. A. Elabd, et al.,
23rd Annual Army Science Conference Oral Paper AO-02 (2002), the
disclosure of which is expressly incorporated herein by reference.
Other examples of separators include electrical insulators, such as
various ceramic materials and polymers (e.g. polyolefin, polyamide,
silicone, polyurethane, polyester and poly(vinyl aromatic)
homopolymers and copolymers, among many others, for example,
TECOTHANE), which provide a way for ions to move through the
separator, for example, due to the presence of pores, holes or
other openings.
[0114] The electrolyte provides mobile charged species (e.g., ions)
which move between the first and second electrodes and which may
participate in the chemical reactions that occur at the electrodes.
Examples of suitable electrolytes include organic and inorganic
salts and acids, such as alkali metal halides and alkaline earth
metal halides, more preferably alkali metal chlorides, such as
potassium chloride or sodium chloride, and acid chlorides such as
HCl. The electrolyte may be supported in ionized form within any
suitable ion supporting medium, including solids, gels and liquids.
Liquids are preferred as supporting media in various embodiments of
the invention. Specific examples of liquids suitable for this
purpose include, for example, polar organic liquids, water, and
mixtures of water and organic liquids.
[0115] For mechanical actuation, the electrolyte may provide ions
(e.g., chloride ions) that participate in electrochemical reactions
that result in bubble formation (e.g., bubbles of oxygen, chlorine,
etc.) upon application of a suitable electric potential across the
first and second electrodes. These bubbles, in turn, cause
expansion of the second electrode.
[0116] One will appreciate that the choice of electrolyte and
supporting medium will be influenced by whether the actuator is to
be open to body fluids or not. For example, diamond-coated
particle-containing regions are frequently porous and may therefore
allow use of blood plasma or other body fluids to supply both the
desired electrolyte (e.g., ions within the blood) and supporting
medium (e.g., water).
[0117] In other embodiments, the actuator components are not open
to the surrounding environment and are therefore provided with an
appropriate electrolyte and supporting medium prior to deployment
of the device. For example, a sheath may be provided which isolates
the actuator components from the outer environment. See, e.g.,
FIGS. 8A and 8B, described above. The sheath may be manufactured
from a variety of materials including, for example, elastomeric
polymer materials. For example, sheaths may be manufactured from
latex rubber, silicon rubber, polyether polyamide block copolymers
such as PEBAX, urethanes such as PELLETHANE and TECOTHANE,
polyesters, polyisobutylene-polystyrene block copolymers, and so
forth. Of course, a porous elastomeric sheath may be employed if
one wishes to use blood plasma or other body fluids as the
electrolyte and supporting medium.
[0118] The power source employed should be capable of applying a
first voltage sufficient for the electrochemical formation of gas
bubbles within the particle-containing conductive region(s), and
may also be capable of applying a second voltage of opposite
polarity from the first voltage that is sufficient to reverse the
electrochemical reactions leading to bubble formation. The power
source may supply, for example, a constant (direct) or variable
(e.g., pulsed) current/voltage. Examples of power sources for
supplying direct current include batteries and rectified
alternating current sources. Voltages on the order of one volt are
sufficient to generate gas within the diamond-coated
particle-containing conductive regions.
[0119] Without wishing to be bound by theory, it is believed that
one or both of the following reactions typically occur during gas
bubble formation: 2Cl.sup.-Cl.sub.2(g)+2e.sup.-E.sub.0=1.12V(vs.
SCE) 2H.sub.2O.fwdarw.O.sub.2(g)+4H.sup.++4e.sup.-E.sub.0=0.99 V
(vs. SCE)
[0120] Gas bubbles are generally observed at the surfaces of the
carbon particles within carbon-particle-containing conductive
regions. Gas bubble formation causes the carbon particles, or
aggregates of the carbon particles (e.g., nanotube "ropes") to move
apart, which in turn causes the volume of the conductive region to
expand. As a specific example, carbon nanotube layers have been
observed to increase in thickness by around 300% (although lesser
and greater percentages are also possible), with the length of the
layer remaining substantially the same. By reversing the polarity,
the reactions may likewise be reversed, causing the
carbon-particle-containing layer to shrink. Kinetically, the
reactions leading to bubble formation and expansion may occur over
a period that is on the order of tens of seconds, whereas the
reactions leading to collapse may occur over a period that is on
the order of a second.
[0121] In general, gas bubbles generated in the interior of the
particle-containing regions are trapped within the region and do
not escape to any significant degree. However, gas bubbles created
at the surface of the conductive region can have a tendency to
escape into the surrounding environment, unless preventative steps
are taken. In the present invention, formation of gas bubbles at
the surface of the particle-containing region is prevented by
providing this region with a diamond-like coating. Unlike the
underlying conductive region, the diamond-like coating is
sufficiently non-conductive to prevent the surface region from
functioning as an active electrode region during the
electrochemical reactions that result in bubble formation.
Consequently, bubbles do not form at the diamond-like coating
surface.
[0122] Although various embodiments are specifically illustrated
and described herein, it will be appreciated that modifications and
variations of the present invention are covered by the above
teachings and are within the purview of the appended claims without
departing from the spirit and intended scope of the invention.
* * * * *